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Biomedical subjects

D Dormont

Publications and source records attributed to D Dormont.

At least 19 recordsLinked to original sources

Neurosurgery at an earlier stage of Parkinson disease: a randomized, controlled trial.

BACKGROUND: Stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson disease (PD) and is currently performed after a mean disease duration of 14 years, when severe motor complications have resulted in marked loss of quality of life. We examined whether surgery at an early stage would maintain quality of life as well as improve motor function. METHODS: Twenty patients with PD of short duration (time elapsed since first symptom +/- SD: 6.8 +/- 1.0 years) with mild to moderate motor signs (Unified Parkinson's Disease Rating Scale III "off" medication: 29 +/- 12) who responded well to levodopa treatment were included in pairs, matched for age, duration and severity of disease, and impairment in socioprofessional functioning. Patients were prospectively randomized to undergo bilateral subthalamic nucleus stimulation (n = 10) or receive optimized medical treatment (n = 10). Parkinsonian motor scores, quality of life, cognition, and psychiatric morbidity were assessed at inclusion and at 6, 12, and 18 months after randomization. RESULTS: Quality of life was improved by 24% in surgical and 0% in nonsurgical patients (p < 0.05). After 18 months, the severity of parkinsonian motor signs "off" medication, levodopa-induced motor complications, and daily levodopa dose were reduced by 69%, 83%, and 57% in operated patients and increased by 29%, 15%, and 12% in the group with medical treatment only (p < 0.001). Adverse events were mild or transient, and overall psychiatric morbidity and anxiety improved in the surgical group. CONCLUSIONS: Subthalamic nucleus stimulation should be considered a therapeutic option early in the course of Parkinson disease.

Activities of Daily Living↗

A volumetric MRI study of the hippocampus and the parahippocampal region after unilateral medial temporal lobe resection.

Segmentation guidelines on high-resolution MRI designed to assess remaining volumes of the hippocampus and the parahippocampal cortices after medial temporal lobe (MTL) surgery could provide a useful tool to investigate the involvement of these anatomical regions in surgical outcomes and in human memory. For this purpose, we implemented an MRI volumetric analysis, already applied to healthy population or epileptic patient before surgery, to quantify the volume of the hippocampus, the temporopolar cortex and the regions of the parahippocampal gyrus (perirhinal, entorhinal and parahippocampal cortices) spared after unilateral MTL resection carried out to treat medically uncontrolled temporal lobe epilepsy (TLE). Based on the locations of remaining anatomical landmarks, we quantified the volume of these regions in 24 patients after MTL resection and in 16 control participants. Our results show that (1) mean volumes of these regions contralateral to the epileptic focus were similar to those of normal subjects, (2) volumetric measures obtained from the resected side were much smaller than those from the non-resected side or from normal values and (3) the extent of MTL resection was comparable in right or left MTL surgery. Individual analysis of patients showed that the parahippocampal cortex, as opposed to the other regions, was not systematically removed across patients. As a post-operative MRI-based method, it therefore proves valuable to assess group data as well as to explore differences between individual patients.

Adult↗

Massive stroke in a patient with pituitary apoplexy, cervical carotid artery stenosis and hypotension.

We report a case of massive cerebral infarct in the early stage of pituitary apoplexy. The case is unique because the stroke was delayed and occurred only after the patient developed severe arterial hypotension superimposed on a tandem internal carotid artery stenosis by both the sellar mass on the siphon and an unknown homolateral atheromatous cervical lesion. Illustrated with MRI and specifically by diffusion-weighted imaging, this case reinforces the idea that a low apparent diffusion coefficient in a non-enhancing sellar mass may indicate the presence of pituitary apoplexy and help in the early adequate management of such patients.

Carotid Artery, Internal↗

Giant solitary fibrous tumour of the meninges: MR-pathological correlation.

The authors present the clinical, MR imaging and pathological features of the largest intracranial solitary fibrous tumour of the meninges ever reported in the literature. This well-circumscribed dural-based tumour strikingly demonstrated two different solid components. The first one demonstrated a suggestive T2 hypointensity that strongly enhanced after gadolinium administration while the other showed more classic homogeneous T2 hyperintensity and mild enhancement. These two components were also identifiable on the pathological examination, allowing an interesting imaging-histological correlation. Differential diagnoses of this rare extra-axial lesion are discussed.

Adult↗

Parkinson disease, brain volumes, and subthalamic nucleus stimulation.

BACKGROUND: High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson disease (PD). The clinical and preoperative predictive factors of the best postoperative outcome have been identified. Radiologic predictive factors were investigated. METHODS: Forty patients with PD underwent surgery for bilateral STN stimulation. MRI was performed in stereotactic conditions before surgery. Brain parenchyma, caudate nucleus, putamen, pallidum, and red nucleus volumes and the surface of the mesencephalon were measured and normalized as percentages of the intracranial volume. Clinical evaluation was performed 1 month before and 6 months after surgery. RESULTS: The normalized brain parenchyma volume was lower in patients who were older and had a longer disease duration or a lower frontal score and was not predictive of the postoperative outcome. The residual scores for activities of daily living and parkinsonian motor disability were higher in patients with a smaller normalized mesencephalon. The normalized caudate nucleus volume was predictive of the pre- and postoperative levodopa-equivalent dosage. CONCLUSIONS: Brain atrophy is not an exclusion criterion for neurosurgery, indicating that patients' neurologic, psychiatric, and neuropsychological characteristics are the best predictive factors for neurosurgery. The fact that a smaller normalized mesencephalon surface was associated with a lower beneficial effect of the subthalamic nucleus stimulation on the parkinsonian motor disability suggests that the normalized mesencephalon surface is a predictive factor of the postoperative outcome.

Activities of Daily Living↗

Acute demyelination: an insight into the effect of mitoxantrone on CNS lesions.

We report the cases of 2 severely disabled patients with large inflammatory lesions suggestive of demyelination treated with mitoxantrone. Clinical condition was improved and brain lesions volume was reduced. On serial MR spectroscopy, there were variations in peaks between 0.9 and 1.4 ppm, suggestive of free lipids and amino acids. These variations may represent neurochemical markers of clinical recovery of large inflammatory lesions in multiple sclerosis.

Acute Disease↗

Macrophage activation switching: an asset for the resolution of inflammation.

Macrophages play a central role in inflammation and host defence against microorganisms, but they also participate actively in the resolution of inflammation after alternative activation. However, it is not known whether the resolution of inflammation requires alternative activation of new resting monocytes/macrophages or if proinflammatory activated macrophages have the capacity to switch their activation towards anti-inflammation. In order to answer this question, we first characterized differential human macrophage activation phenotypes. We found that CD163 and CD206 exhibited mutually exclusive induction patterns after stimulation by a panel of anti-inflammatory molecules, whereas CCL18 showed a third, overlapping, pattern. Hence, alternative activation is not a single process, but provides a variety of different cell populations. The capacity of macrophages to switch from one activation state to another was then assessed by determining the reversibility of CD163 and CD206 expression and of CCL18 and CCL3 production. We found that every activation state was rapidly and fully reversible, suggesting that a given cell may participate sequentially in both the induction and the resolution of inflammation. These findings may provide new insight into the inflammatory process as well as new fields of investigation for immunotherapy in the fields of chronic inflammatory diseases and cancer.

Anti-Inflammatory Agents↗

Tourette's syndrome and deep brain stimulation.

In this prospective double blind randomised "N of 1" study, a patient with a severe form of Tourette's syndrome was treated with bilateral high frequency stimulation of the centromedian-parafascicular complex (Ce-Pf) of the thalamus, the internal part of the globus pallidus (GPi), or both. Stimulation of either target improved tic severity by 70%, markedly ameliorated coprolalia, and eliminated self injuries. Severe forms of Tourette's syndrome may benefit from stimulation of neuronal circuits within the basal ganglia, thus confirming the role of the dysfunction of limbic striato-pallido-thalamo-cortical systems in this disorder.

Adult↗

Stimulation of the subthalamic nucleus in Parkinson's disease: a 5 year follow up.

BACKGROUND: The short term benefits of bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced levodopa responsive Parkinson's disease (PD) are well documented, but long term benefits are still uncertain. OBJECTIVES: This study provides a 5 year follow up of PD patients treated with stimulation of the STN. METHODS: Thirty seven consecutive patients with PD treated with bilateral STN stimulation were assessed prospectively 6, 24, and 60 months after neurosurgery. Parkinsonian motor disability was evaluated with and without levodopa treatment, with and without bilateral STN stimulation. Neuropsychological and mood assessments included the Mattis Dementia Rating Scale, the frontal score, and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: No severe peri- or immediate postoperative side effects were observed. Six patients died and one was lost to follow up. Five years after neurosurgery: (i) activity of daily living (Unified Parkinson Disease Rating Scale (UPDRS) II) was improved by stimulation of the STN by 40% ("off" drug) and 60% ("on" drug); (ii) parkinsonian motor disability (UPDRS III) was improved by 54% ("off" drug) and 73% ("on" drug); (iii) the severity of levodopa related motor complications was decreased by 67% and the levodopa daily doses were reduced by 58%. The MADRS was unchanged, but cognitive performance declined significantly. Persisting adverse effects included eyelid opening apraxia, weight gain, addiction to levodopa treatment, hypomania and disinhibition, depression, dysarthria, dyskinesias, and apathy. CONCLUSIONS: Despite moderate motor and cognitive decline, probably due to disease progression, the marked improvement in motor function observed postoperatively was sustained 5 years after neurosurgery.

Activities of Daily Living↗

N-butyl 2-cyanoacrylate embolization of spinal dural arteriovenous fistulae: CT evaluation, technical features, and outcome prognosis in 26 cases.

BACKGROUND AND PURPOSE: This study investigated the role of CT as an early predictor of outcome prognosis after glue embolization of spinal dural arteriovenous fistulas (SDAVF). METHODS: Over a 13-year period, 26 patients underwent glue embolization of SDAVF and were retrospectively reviewed. Immediately after embolization, each patient had CT evaluation of cast position. Mean follow-up angiography was 23.4 months (range, 1-87 months; median, 21 months). Both MR images and clinical data (e.g., gait and micturition disabilities according to the Aminoff and Logue disability scale, deep and superficial sensitivity) were analyzed, with a mean follow-up of 37.7 months (range, 12-98 months; median, 28 months). Data were tested by univariate analysis by using Fisher's exact test and the Kruskall Wallis test, depending on the order of the qualitative variables. RESULTS: Glue was found in the dura mater on CT in 19 (73%) patients. None of these patients had a recanalized fistula on angiography, and the clinical status of all of them improved. Glue was observed in or proximal to the foramen on CT in seven (27%) patients. In five of them, the fistula was recanalized within a mean period of 9 months (range, 3-24 months; median, 6 months) and their clinical status worsened. All five required surgical treatment. On angiography, the absence of fistula recanalization was observed in 21 (81%) patients and correlated with improvements in gait (P = .016), sensitivity (P = .030), and micturition (P = .080). It also correlated with a decrease in the extent of the abnormally high intramedullary T2 signal intensity (P = .002), a decrease in spinal cord diameter (P = .017), and the resolution of prominent perimedullary vessels (P < .001). The presence of glue within the dura mater on CT correlated with the absence of fistula recanalization (P = .045) and with overall improvement in clinical status, including gait and/or sensitivity and/or micturition (P = .042). CONCLUSION: CT evaluation of embolization cast position immediately after embolization may constitute an early and reliable tool for predicting permanent fistula occlusion and the prognosis for outcome.

Adult↗

Tissue distribution of bovine spongiform encephalopathy agent in primates after intravenous or oral infection.

BACKGROUND: The disease-associated form of prion protein (PrP(res)) has been noted in lymphoreticular tissues in patients with variant Creutzfeldt-Jakob disease (vCJD). Thus, the disease could be transmitted iatrogenically by surgery or use of blood products. We aimed to assess transmissibility of the bovine spongiform encephalopathy (BSE) agent to primates by the intravenous route and study its tissue distribution compared with infection by the oral route. METHODS: Cynomolgus macaques were infected either intravenously or orally with brain homogenates from first-passage animals with BSE. They were clinically monitored for occurrence of neurological signs and killed humanely at the terminal stage of the disease. Brain, lymphoreticular tissues, digestive tract, and peripheral nerves were obtained and analysed by sandwich ELISA and immunohistochemistry for quantitative and qualitative assessment of their PrP(res) content. FINDINGS: Incubation periods after intravenous transmission of BSE were much shorter than after oral infection. We noted that PrP(res) was present in lymphoreticular tissues such as spleen and tonsils and in the entire gut from the duodenum to the rectum. In the gut, PrP(res) was present in Peyer's patches and in the enteric nervous system and nerve fibres of intestinal mucosa. Furthermore, PrP(res) was found in locomotor peripheral nerves and the autonomic nervous system. Amount of PrP(res) ranged from 0.02% to more than 10% of that recorded in brain. Distribution of PrP(res) was similar in animals infected by the intravenous or oral route. INTERPRETATION: Our findings suggest that the possible risk of vCJD linked to endoscopic procedures might be currently underestimated. Human iatrogenic vCJD cases infected intravenously raise the same public-health concerns as primary cases and need the same precautionary measures with respect to blood and tissue donations and surgical procedures.

Administration, Oral↗

First-line intraperitoneal cisplatin-paclitaxel and intravenous ifosfamide in Stage IIIc ovarian epithelial cancer.

OBJECTIVES: To determine the feasibility, toxicity and efficacy of a first-line combination of intraperitoneal (i.p.) paclitaxel and cisplatin and intravenous (i.v.) ifosfamide in untreated patients with Stage IIIc ovarian cancer after cytoreduction or biopsies only. METHODS: Twenty-six patients entered the trial from 1995 to 1999. Twenty underwent initial cytoreduction which was complete, with residual nodules < 0.5 cm or = 0.5 cm in six, five and nine patients, respectively. Six patients underwent biopsies only at initial surgery. Ten cycles of chemotherapy were planned by both routes. Second-look surgery was planned for all patients. RESULTS: Twenty-one (81%) of the 26 patients were in complete clinical remission (CCR) at the time of second-look surgery. Of the 15 patients who underwent second-look surgery, ten were in CCR including seven in complete remission (CR) confirmed pathologically. Median overall-survival had not been reached at 53 months (range 16-87), and median disease-free survival was 40 months (range 8-85), for a median follow-up of 53 months (range 16-87). Local toxicity consisted mainly of mild abdominal pain. Systemic toxicity was essentially haematological, with eight (31%) grade 3-4 leukopenia. CONCLUSION: This study has demonstrated the feasibility, moderate toxicity and efficacy of first-line intraperitoneal paclitaxel-cisplatin chemotherapy.

Adenocarcinoma, Mucinous↗

Quinolinic acid up-regulates chemokine production and chemokine receptor expression in astrocytes.

Within the brain, quinolinic acid (QUIN) is an important neurotoxin, especially in AIDS dementia complex (ADC). Its production by monocytic lineage cells is increased in the context of inflammation. However, it is not known whether QUIN promotes inflammation. Astrocytes are important in immuno-regulation within the brain and so we chose to examine the effects of QUIN on the astrocyte. Using purified cultures of primary human foetal astrocyte, we determined chemokine production using ELISA assays and RT-PCR, and chemokine receptor expression using immunocytochemistry and RT-PCR with QUIN in comparison to TNF-alpha/IFN-gamma. We found that QUIN induces astrocytes to produce large quantities of MCP-1 (CCL2), and lesser amounts of RANTES (CCL5), IL-8 (CXCL8). QUIN also increases SDF-1alpha (CXCL12), HuMIG (CXCL9) and fractalkine (CX3CL1) mRNA expression. Moreover, QUIN leads to up-regulation of the chemokine receptor expression of CXCR4, CCR5, and CCR3 in human foetal astrocytes. Most of these effects were comparable to those induced by TNF-alpha/IFN-gamma. The present work represents the first evidence that QUIN induces chemokine and chemokine receptor expression in astrocytes and is at least as potent as classical mediators such as inflammatory cytokines. These results suggest that QUIN may be critical in the amplification of brain inflammation particularly in ADC.

Astrocytes↗

Decreases in plasma TNF-alpha level and IFN-gamma mRNA level in peripheral blood mononuclear cells (PBMC) and an increase in IL-2 mRNA level in PBMC are associated with effective highly active antiretroviral therapy in HIV-infected patients.

In this study, we investigated the cytokine profiles of 14 treatment-naive HIV-infected patients on the initiation of highly active antiretroviral therapy (HAART). At baseline, plasma levels of TNF-alpha and its mRNA in peripheral blood mononuclear cells (PBMC) were highest in the most severely immunocompromised patients (<200 CD4+ cells/mm3). After 12 months of HAART, the virus was undetectable in the plasma of all patients (<200 copies/ml), and median CD4 T cell counts had increased (+164 cells/mm3). We also observed a gradual decrease in the number of proviral DNA copies in PBMC and in immune activation, with lower levels of IFN-gamma mRNA in PBMC associated with weaker activation of CD8+ T cells and lower levels of plasma TNF-alpha. IL-2 mRNA levels in PBMC were found to increase in parallel. The decrease in TNF-alpha and IFN-gamma levels and the increase in IL-2 production appear to be correlated with the efficacy of HAART in naive immunocompromised HIV-infected individuals.

Adult↗

[Intracerebral hematoma associated with reduced apparent diffusion coefficient mimicking acute stroke].

We report the case of a 67 year old patient admitted at our institution for acute onset of left hemiplegia. MRI was done 2 h 30 after symptom onset. Diffusion weighted images showed a hyperintense lesion in the right basal ganglia region with restricted apparent diffusion coefficient (ADC=428. 10(-6) mm(2)/s), a 50% decrease in value compared to the normal left side, consistent with acute ischemia. The lesion was hyperintense and moderately heterogeneous at FLAIR imaging, best seen on echo planar T2W images, with hypointense rim consistent with magnetic susceptibility artifact. The appearance and location of the lesion suggested the possibility of hematoma, which was confirmed at CT. Interpretation of ADC values must be performed in correlation with results at imaging including sequences sensitive to magnetic susceptibility artifacts such as echo planar T2*W and T2W sequences in order to exclude the possibility of underlying hematoma.

Acute Disease↗

[Disinfection of gas-permeable contact lenses against prions].

Potential iatrogenic transmission from patients incubating Creutzfeldt-Jakob disease, especially variant CJD, is a major public health issue. Because the ocular route is very efficient for contamination with prions, re-use of rigid contact lenses in ophthalmology constitutes a potential problem. We therefore evaluated the anti-prion activity of different protocols available for disinfection of lenses. These treatments decreased the infectivity retained on the surface of experimentally contaminated lenses by a factor of at least 10 million. They thus represent an important factor in protecting against possible prion infection via the ocular route.

Animals↗

[Rathke's cleft cyst].

Rathke's cleft cyst (RCC) are frequent benign cystic sellar lesions. Most RCC are small, intrasellar and asymptomatic. Larger cysts may compress adjacent structures and rarely become symptomatic. Diagnosis is strongly suggested at MRI by the presence of a midline non-enhancing lesion located exactly between the anterior and posterior lobes of the pituitary gland. Even if its signal is variable and related to intracystic protein concentration, it must be homogeneous with no fluid-fluid level. Once a diagnosis of RCC made, routine MR and clinical follow-up is sufficient for incidental asymptomatic cysts whereas the rare symptomatic lesions are neurosurgically resected.

Central Nervous System Cysts↗